Synaptic plasticity in the dy2J mouse model of laminin α2-deficient congenital muscular dystrophy

Laminin alpha 2-deficient congenital muscular dystrophy is a debilitating disease affecting both muscle and neural tissue as a result of mutations in the LAMA2 gene. It presents at or soon after birth with muscle weakness and is further characterised by clinical central nervous system involvement. Laminin alpha 2 is part of the extracellular matrix, linked to the cellular cystoskeleton via dystroglycan which is an integral part of the dystrophin-glycoprotein complex (DGC). We examined both short- and long-term synaptic plasticity in the C57BL6J/dy(2J) mouse, an animal model of laminin alpha 2 deficient congenital muscular dystrophy. Using a cerebellar slice preparation, we show that the presynaptically mediated paired-pulse facilitation (PPF) was no different between dy(2J) and littermate controls. Approximately half (7/12) the dy(2J) Purkinje cells displayed a blunted LTD compared to littermate controls, and one third (4/12) of dy(2J) Purkinje cells displayed LTP. This study demonstrates that a defective laminin alpha 2 causes a disruption in long-term synaptic plasticity at the Purkinje cell-parallel fibre synapse. Crown Copyright (c) 2005 Published by Elsevier B.V. All rights reserved.